Associated or combined vaccination of Brazilian infants with a conjugate Haemophilus influenzae type b (Hib) vaccine, a diphtheria-tetanus-whole-cell pertussis vaccine and IPV or OPV elicits protective levels of antibodies against Hib.

This study investigated the immunogenicity and safety of including a Haemophilus influenzae type b vaccine (polyribosylribitol phosphate conjugated to tetanus toxoid, PRP-T) in three different vaccination schemes: (1) PRP-T reconstituted with a combined diphtheria-tetanus-pertussis-inactivated poliovirus vaccine (DTP-IPV//PRP-T); (2) PRP-T reconstituted with DTP and administered concomitantly with an oral poliovirus vaccine (DTP//PRP-T+OPV); and (3) PRP-T administered concomitantly with DTP at a different injection site and OPV (DTP+PRP-T+OPV). Vaccines were given at 2, 4, and 6 months of age. A total of 252 infants were enrolled, and randomly assigned to one of the three vaccination groups (84 infants in each group); 241 infants were followed until the end of the study. Antibody production against PRP, diphtheria, tetanus and pertussis antigens was satisfactory for each vaccination scheme used. A good response to Hib vaccine was elicited in each group, and 3 months after the third vaccine dose, at least 97% of children in each group had levels of PRP antibody considered to be seroprotective (>0.15 microg/ml), and over 90% of children in each group had levels over 1. 0 microg/ml. The solicited local and systemic adverse events following vaccination were mild in all groups and resolved within 4 days without medical intervention. With the exception of fever, which was more common after the second dose in children who received DTP-IPV//PRP-T, local and systemic reactions did not differ between the vaccination groups. Due to the practical advantages of combined vaccines, their use in routine immunization programs in developing countries is highly desirable. Our results show that Hib conjugate vaccine can be included in routine immunization programs that include either OPV or IPV with satisfactory immunogenicity and safety profiles. This flexible approach should facilitate the inclusion of the Hib conjugate vaccine in routine immunization programs on a world-wide scale.

Evaluation of serum levels of IgG subclasses and anti-ribosyl-ribitolphosphate IgG and IgG2 in children with Haemophilus influenzae b meningitis.

In 40 children with Haemophilus influenzae b (Hib) meningitis, we determined serum levels (mg/dl) of IgG subclasses using the radial immunodiffusion method; 67.8 per cent of these children were less than 24 months old. In 14 children of the sample we measured serum IgG and IgG2 anti-ribosyl-ribitolphosphate (anti-PRP) (by enzyme-linked immunosorbent assay, ELISA) in the acute and convalescent phases of the disease. Lower IgG2 levels than those of the control group were obtained in all age ranges: 3-12 months, 1-2 years (p < 0.01), and 2-5 years (p < 0.001). IgG4 was also present in lower levels in patients of all age ranges (p < 0.05, p < 0.001, and p < 0.01 respectively). Serum levels of IgG anti-PRP and IgG2 anti-PRP measured were very low in the acute phase of the disease in all age ranges and there was no notable increase in levels during the convalescent phase of the disease. This result indicates that children less than 24 months old do not produce sufficient levels of IgG and IgG2 anti-PRP even after Hib meningitis.

Human serum beta2-microglobulin levels: correlation with total serum IgG and placental IgG transfer in HIV-infected and non-HIV infected individuals.

The acquisition of maternal immunoglobulin G (IgG) is fundamental to the immune defence of the neonate. The receptor responsible for IgG transfer across the human placenta has also been implicated in the maintenance of IgG levels in the circulation. beta2-microglobulin is part of the Fc receptor (FcR) that has recently been purified from the human placenta. In HIV infection, increasing serum levels of total IgG and beta2-microglobulin are observed as the disease progresses. Herein, we have investigated the correlation between beta2-microglobulin and total serum IgG levels in HIV-seropositive mothers and their term neonates (HIV group, n = 37), as well as in HIV-seronegative mothers and their term neonates (control group, n = 50). Serum maternal beta2-microglobulin was directly correlated with total serum IgG levels in HIV-infected mothers (r = 0.58; P = 0.0002), but not in healthy HIV-seronegative mothers (r = -0.20; P = 0.16). Maternal serum beta2-microglobulin was also inversely correlated with placental antibody transfer of total IgG in mother-newborn pairs from the HIV group (r = 0.38; P = 0.02), but not from the control group (r = 0.15. P = 0.31). These results seem to indicate that, in HIV infection, elevated serum beta2-microglobulin levels could be involved in maintenance of abnormally high total serum IgG concentrations; by interfering with the binding of IgG to Fc receptors at the maternal-fetal interface, they might also reduce IgG transfer. By contrast, in normal non-HIV infected individuals, serum beta2-microglobulin levels do not appear implicated in regulation of these two phenomena.

[Bacterial meningitis - diagnosis and treatment] / Meningites bacterianas - diagnóstico e conduta.

OBJECTIVE: To present new concepts on diagnosis and treatment of bacterial meningitis regarding etiologic agents, pathophysiology and options about antimicrobial, antiinflammatory and supportive therapy. METHODS: Bibliographic review from MEDLINE data including articles published during the last ten years. One classic article published before this period and chapters of textbooks on infectious diseases were also included. RESULTS: Initial empirical antibiotic therapy is chosen according to probable etiologic agents for the age group. In the CSF microbiological analysis, the gram stains can reveal bacteria in 50% to 80% of the cases and the culture in nearly 85%. The tests for detection of bacterial antigens are useful for the diagnosis but they present low sensitivity. The most common agents during the neonatal period continue to be E. coli, Streptococcus B and L. monocytogenes. Beyond this period, the incidence of meningitis by Haemophilus influenzae b had a significant decrease after the introduction of conjugate vaccines. However, S. pneumoniae and N. meningitidis continue to be frequent agents. Currently, the thirdgeneration cephalosporins, ceftriaxone or cefotaxime, are the antibiotic therapy of choice. They are used with ampicillin up to two months of life and alone beyond this age. Dexamethasone has showed to be effective in reducing the inflammatory response and the sequelae, mainly the auditory sequelae. The fluid restriction doesn't offer advantages in the supportive care. CONCLUSIONS: Early diagnosis and prompt treatment are related to good outcome. The new insights on pathophysiology, the new antibiotics and the increasing bacterial resistance have determined changes in treatment.

[Acquired toxoplasmosis] / Toxoplamose adquirida.

OBJECTIVE: The aim of this review is to present some important aspects of acquired toxoplasmosis to the pediatric practitioner. METHOD: All the articles about acquired toxoplasmosis published during the last decade and indexed in the Index Medicus were revised. From each one, interesting aspects were critically selected. RESULTS: We describe aspects of the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment and prevention related to acquired toxoplasmosis. CONCLUSION: The content of this article may facilitate the management of patients suspected of having acquired toxoplasmosis.

Seroconversion of a trivalent measles, mumps, and rubella vaccine in children aged 9 and 15 months.

The serological response to MMR vaccine was evaluated in 109 9-month-old infants having no history of measles vaccination, and in 98 15-month-old children who had received monocomponent measles immunisation at 9 months. The combined vaccine contained Schwarz, Urabe Am9, and Wistar RA 27/3 live attenuated virus strains. Preimmunisation antibody levels were extremely low for the 9-month-old children, indicating that maternally-transmitted antibodies do not persist at this age. In the case of mumps, preimmunisation antibody levels were significantly higher in the 15-month-old than in the 9-month-old group. A difference between groups in terms of postimmunisation antibody titres was observed only for rubella, with titres being significantly higher in the older group. Seroconversion rates were high in both groups and no serious events attributable to vaccination were observed. The MMR vaccine can thus be administered to children as young as 9 months of age. Evidence for the efficacy of a two-dose schedule, i.e. at 9 and 15 months, is presented.

[Prevalence of Haemophilus influenzae resistant to ampicillin, cefaclor, cefotaxime, chloramphenicol and cotrimoxazol isolated from laboratories in the city of São Paulo, Brazil]. / Prevalência de Haemophilus influenzae resistentes a ampicilina, cefaclor, cefotaxime, cloranfenicol e cotrimoxazol isolados de laboratórios na cidade de São Paulo.

OBJECTIVE: To determine Haemophilus influenzae resistant to ampicillin and other antibiotics isolated from different clinical specimens. METHODS: Isolates of H. influenzae were identified by culture with V and X factors and the aminolevulinic test. Nitrocefin was used to detect beta-lactamase (betaLac) production isolates were tested for antimicrobial susceptibility by disc diffusion and agar dilution methods. Serotype b was assessed by slide co-agglutination. RESULTS: From 245 H. influenzae identified, 155 were tested for serotype b, 28% (43/155) of which were positive. The global rate of beta-lactamase-positive isolates was 9% (22/245). Resistance was similar among serotype b (11.6%) and non-type b H. influenzae (9.8%) (p>0.05). No difference on betaLac production was found according to specimen's origin or the patients' age. Resistances to other antibiotics (by agar dilution and disc diffusion method, respectively) were: chloramphenicol 3.3 to 7.1%; cefaclor: 1.6 to 3.9% and cotrimoxazol: 9.1 to 10.5%. No resistance to cefotaxime has been detected; 63% (5/8) beta-Lac-positive isolates by agar dilution showed also resistance to chloramphenicol, compared to 3% (4/118) in the ss-Lac-negative group (p<0.001). CONCLUSIONS: H. influenzae ampicillin-resistance has shown to be lower than other hospital-based-studies in São Paulo, and comparable to rates found in healthy carriers. The association between ampicillin and chloramphenicol resistance was significant: where this pattern is frequently found, the initial therapy for severe H. influenzae infections - like meningitis - should include a third generation cephalosporin.

[Comparison of seroconversion rates between well-nourished and malnourished children after measles immunization at nine months of age]. / Viragem sorológica após a vacinação contra o sarampo, realizada em crianças eutróficas e desnutridas, aos nove meses de idade.

The study was based on activities developed at Embu, SP, between October 1989 and June 1990. Its purpose was to study serological turning after child vaccination against measles at the age of nine months. Two groups were compared, both within the same age limits. Group number I included eutrophic children and group number II included undernourished children. Gomes criteria was used to evaluate the childrens nutritional state. Antibodies (AB) dosage was done through hemagglutination inhibition (HI) and ELISA. These two laboratory methods were also checked regarding its sensibility. Out of 130 children studied, 80 could be evaluated. From this total, 56 (70%) belonged to group I and 24 (30%) belonged to group II. When the ELISA method was used, a significantly higher seroconversion percentage (P < 0.05 or 5%) was found among children belonging to group II. This percentage was not detected when the HI method was used.

Placental transfer and maternally acquired neonatal IgG immunity in human immunodeficiency virus infection.

Transplacental transfer of specific IgG antibodies was studied in 46 pairs of human immunodeficiency virus type 1 (HIV-1)-seropositive women and their neonates and in 53 pairs of healthy HIV-seronegative mothers and their newborns. Neonatal and maternal sera were assessed by nephelometry for total levels of serum IgG and by ELISA for IgG antibodies to herpes simplex virus (HSV), varicella-zoster virus (VZV), measles virus, tetanus toxoid, streptolysin O, and Streptococcus pneumoniae capsular antigens. Placental transfer of IgG antibodies to VZV, tetanus toxoid, measles, streptolysin O, and S. pneumoniae was decreased by maternal HIV infection. Maternal levels of total IgG had an independent effect on transfer of antibodies to HSV, VZV, measles, and S. pneumoniae. Neonatal antibody levels to tetanus toxoid, measles, and S. pneumoniae were significantly lower in the HIV group. Both maternal hypergammaglobulinemia and maternal HIV infection may contribute to these low antibody levels at birth and thus lead to early infection in this high-risk population.

The antimeningococcal vaccine VAMENGOC B-C induced poor serum and salivary antibody response in young Brazilian children.

In 1989 about 2.3 million Brazilian children received the antimeningococcal vaccine VAMENGOC B-C (Havana, Cuba). We evaluated the serum and secretory immune response of vaccinated children by enzyme-linked immunosorbent assay with outer membrane complex antigens. Western blotting and bacterial adherence inhibition assays with human buccal epithelial cells were performed with some of the samples. Serum and salivary antibody concentrations to Neisseria meningitidis Group B of vaccinated children < 4 years old were not significantly higher than those of nonvaccinated children, as observed in convalescing patients used as positive controls. Older children (4 to 6 years old) presented a slight increase in antibody OD indexes. Sera and saliva from vaccinated children showed a weak reaction with meningococcal antigen by Western blotting and were unable to inhibit significantly the adherence of N. meningitidis B to buccal epithelial cells. These data suggest that this vaccine induced a poor serum and salivary antibody response in the population studied.

[BCG test reaction in previously BCG Moreaux-Rio de Janeiro-vaccinated healthy children]. / BCG-teste em crianças sadias previamente vacinadas com a BCG Moreaux-Rio de Janeiro.

BCG-test reaction was carried out in 91 non-tuberculous children between 2 and 11 years old, who had received BCG vaccination during the first six months of life to critically evaluate the usefulness of this test in Pediatric practice. The BCG-test profile of the vaccinated group was shown to have a unimodal distribution, varying from 3 to 17 millimeters, with a median of 6 millimeters. It was demonstrated that the degree of reaction decreases with time. Nevertheless, false-positives could be expected in a significant percentage when reactions larger than 10 millimeters are considered as a cutoff. The specificity can be increased using only reactions with diameter equal or greater than 15 millimeters as an indicator of tuberculous disease.

Maternally acquired immunity in newborns from women infected by the human immunodeficiency virus.

Maternally acquired immunity was studied in 16 pairs of human immunodeficiency virus (HIV)-seropositive women and their newborns, and was compared to 18 control mother-newborn pairs. The HIV-infected women had higher IgG levels than the control subjects, but no difference was observed between newborn samples, presumably due to the limited placental IgG transfer in the HIV group. A poor type 2 poliovirus antibody transfer was also noted in this group. The population of newborns lacking demonstrable measles antibodies was higher in the HIV group than in the control group, probably because many of the HIV-infected mothers lacked measles antibodies also. These results show that maternally acquired immunity may be affected to newborns from HIV-infected women, either because of low maternal serum antibody levels or deficient transplacental transfer. If so, the measles vaccine schedule should be revised for these children and the same should be done for future passive immunization regarding fetus protection in pregnant HIV-seropositive women.

Cerebrospinal fluid levels of lysozyme, IgM and C-reactive protein in the identification of bacterial meningitis.

Lysozyme (LZM), immunoglobulin M (IgM) and C-reactive protein (CRP) levels were determined in cerebrospinal fluid (CSF) from patients classified on the basis of clinical and laboratory findings into three groups: bacterial meningitis (n = 33), lymphocytic meningitis (n = 21) and controls (n = 54). IgM and CRP levels were determined by enzyme-linked immunosorbent assay (ELISA) and LZM by the lysoplate method. Discriminant analysis demonstrated that 93.94% (31/33) and 96.97% (32/33) of patients with bacterial meningitis were correctly classified on the basis of CSF determinations of IgM and LZM, respectively. However, the measurement of CRP levels in CSF correctly classified 100% of these patients (33/33), thus representing a useful additional marker for the screening of bacterial meningitis. Moreover, no more than 4% (3/75) of patients were incorrectly classified as belonging to the bacterial group on the basis of the CRP test. Thus, CRP titres less than or equal to 80 identify cases belonging to one of the non-bacterial groups, whereas titres greater than or equal to 640 classify the bacterial group, with a very low chance of misclassification. The authors recommend that CSF IgM or LZM levels be also measured for patients with CSF CRP titres of 160 and 320, for a more accurate diagnosis. The probability of these cases being of bacterial aetiology, as calculated from the combined results of these measurements, is presented.

Ceftriaxona em meningites na infância: possibilidade de tratamento ambulatorial / Ceftriaxone in miningitis childhood

Devido ao amplo espectro antimicrobiano e seu esquema de dose única diária, a ceftriaxona tem sido largamente usada para o tratamento de infecçöes graves, incluindo meningite bacteriana. Entre os importantes problemas enfrentados por médicos e pacientes em países desenvolvidos, estäo a falta de leitos hospitalares e a alta incidência de hospitalares. Por estas razöes e baseados em nossa experiência prévia com o uso de ceftriaxona, decidimos estudar a possibilidade de um regime terapêutico que permitisse tratamento ambulatorial de pacientes com meningite bacteriana. Vinte crianças com idades variando entre 3 e 75 meses e com diagnóstico de meningite bacteriana causada por N. meningitidis, S. pneumoniae ou H. influenzae, foram tratadas com dose única...

[Persistence of colonization time in patients infected by Salmonella]. / Estudo da persistência de colonização em pacientes infectados por Salmonella.

Salmonella is an important etiological agent of hospital infection in children, reaching endemic levels in some Brazilian states during the seventies and the eighties. We have prospectively studied twenty five children between four and one hundred eighty days old acutely infected with salmonella non typhi to determine the duration of carrier status and its clinical repercussion. After the diagnosis, the children were submitted monthly to clinical examination, and cultures were collected from skin, oropharynx, urine, stools, genitals, nostrils and auditive conduct. During the follow-up, eighteen (72%) children still had positive culture at four weeks after the diagnosis, ten (40%) at sixteen weeks, four (16%) at twenty weeks, and one (4%) at twenty four weeks. In eleven children, we performed biotype and antibiotic susceptibility study of the bacteria recovered at the diagnosis and during the follow-up. In every child the biotype of the bacteria recovered at the diagnosis and during the follow-up was the same. These data indicate that there is a persistent excretion of salmonella that can last for 24 weeks. Such bacterial elimination may be a dissemination source either to hospital or to home contacts. The use of specific antibiotics was effective for the clinical improvement of the patients during the acute disease, but it didn't avoid the carrier state.